In order to understand the control of gene expression in higher eukaryotes, we are studying how exogenous DNA (genes) are integrated and expressed in mouse cells. We are investigating the process by which the DNA is integrated. Among the many questions being asked are: (1) what is the DNA into which the first integration occurs; (2) are there specific sequences that promote this recombination; and (3) does the integrated DNA have a mutagenic (or carcinogenic) effect on the host cell. We are also analyzing the expression of the herpes thymidine kinase gene transferred into mouse L cells. In some cases the phenotype appears to be quickly reverting from thymidine kinase positive (tk-plus) to tk-minus and back to tk-plus. DNA-mediated gene transfer is also being used to purify selected genes of particular biomedical interest.